Leukemia
Conditions
Keywords
Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia
Brief summary
RATIONALE: Vaccines made from a peptide may help the body build an effective immune response to kill cancer cells. PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with chronic phase chronic myelogenous leukemia.
Detailed description
OBJECTIVES: * Determine the antileukemic effects of tumor-specific Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) junction specific peptide vaccine, as measured by a decrease in circulating BCR-ABL transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR), that persist for at least 3 months, in patients with chronic phase chronic myelogenous leukemia. * Determine the percentage of patients treated with this vaccine who become RT-PCR-negative for BCR-ABL transcripts. * Compare response in patients with B3A2 junctions vs B2A2 junctions when treated with this vaccine. * Determine the immunologic response over 1 year in patients treated with this vaccine. * Correlate response with specific HLA types in these patients. * Determine the safety of this vaccine in these patients. OUTLINE: This is a pilot, multicenter study. Patients receive BCR-ABL junction-specific peptide vaccine subcutaneously in weeks 2, 4, 6, 8, and 11 and then once monthly for 10 months. BCR-ABL transcript levels are assessed by quantitative reverse-transcriptase polymerase chain reaction at baseline, weeks 2, 4, and 6, every 3 months during treatment, and then 2 weeks after completion of study treatment. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Interventions
BIOLOGICALbcr-abl peptide vaccine
Patients will be vaccinated 15 times over 12 months with a vaccine comprised of native and synthetic break-point cluster region-Abelson murine leukemia(BCR-ABL) specific peptides and the immunologic adjuvants, Montanide ISA 51-VG.
GENETICreverse transcriptase-polymerase chain reaction
A baseline reverse transcriptase-polymerase chain reaction(RT-PCR) transcript level of BCR-ABL will be determined after enrollment on study. This baseline will be used to measure response to the vaccine. Patients will have 3 quantitative RT-PCR tests for BCR-ABL transcript levels performed on their peripheral blood in the first month after enrolling on study. Peripheral blood samples will be drawn at approximately 1-month prior (about day -30), 2 weeks prior (about day -14), and the day of the first vaccination (day 0). Samples will be analyzed at a central lab and the three values will be averaged to determine a baseline circulating transcript level. During this one-month period, a peripheral blood sample will be analyzed to determine whether patients have a B3A2 or B2A2 junction.
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of Philadelphia chromosome-positive or BCR-ABL-positive chronic phase chronic myelogenous leukemia (CML) * In complete cytogenetic remission confirmed by 2 bone marrows ≥ 1 month apart * Minimal residual disease * Detectable BCR-ABL transcript levels obtained \< 6 months apart AND ≤ 0.5-log lower than the lowest value obtained within the past 6 months PATIENT CHARACTERISTICS: * Karnofsky performance status 80-100% * Bilirubin \< 2 times upper limit of normal (ULN) * Creatinine \< 1.5 times ULN * ALT and AST \< 2.5 times ULN PRIOR CONCURRENT THERAPY: * Recovered from prior therapy * No major surgery within the past 4 weeks * No prior chemotherapy * No prior immunosuppressive therapy * No prior corticosteroids * No prior stem cell transplantation * No radiotherapy within the past 4 weeks * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One-log Decrease in Circulation Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) Transcripts That Persists for at Least Three Months During the 1-year Treatment Period. | Every 3 months for the duration of the 1-year treatment period. . | One-log decrease in circulating BCR-ABL transcripts (RT-PCR) that persists for at least three months during the 1-year treatment period. |
| Percentage of Patients Who Become RT-PCR-negative for BCR-ABL Transcripts | 12-24 Months | — |
| Comparison of Response in Patients With B3A2 Junctions vs B2A2 Junctions | 12-24 Months | — |
| Immunologic Response Over 1 Year | 12 months | — |
| Correlation of Response With Specific HLA Types | 12-24 Months | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety of a Vaccine Containing Native and Synthetic Chronic Myeloid Leukemia (CML) Peptides Over 1 Year Treatment. | Weeks 2, 4, 6, 9, and monthly thereafter up to 2 years. |
Countries
United States
Participant flow
Recruitment details
Recruited from patient database in medical clinic.
Participants by arm
| Arm | Count |
|---|---|
| Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) Patients will be vaccinated 15 times over 12 months with a vaccine comprised of native and synthetic BCR-ABL (break-point cluster region-Abelson murine leukemia) specific peptides and the immunologic adjuvants, Montanide ISA 51-VG. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age Continuous | 59.75 years STANDARD_DEVIATION 3.59 |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Comparison of Response in Patients With B3A2 Junctions vs B2A2 Junctions
Time frame: 12-24 Months
Primary
Correlation of Response With Specific HLA Types
Time frame: 12-24 Months
Primary
Immunologic Response Over 1 Year
Time frame: 12 months
Primary
Number of Participants With One-log Decrease in Circulation Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) Transcripts That Persists for at Least Three Months During the 1-year Treatment Period.
One-log decrease in circulating BCR-ABL transcripts (RT-PCR) that persists for at least three months during the 1-year treatment period.
Time frame: Every 3 months for the duration of the 1-year treatment period. .
Population: Per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) | Number of Participants With One-log Decrease in Circulation Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) Transcripts That Persists for at Least Three Months During the 1-year Treatment Period. | 4 Participants |
Primary
Percentage of Patients Who Become RT-PCR-negative for BCR-ABL Transcripts
Time frame: 12-24 Months
Secondary
Safety of a Vaccine Containing Native and Synthetic Chronic Myeloid Leukemia (CML) Peptides Over 1 Year Treatment.
Time frame: Weeks 2, 4, 6, 9, and monthly thereafter up to 2 years.